1. Field of the Invention
The present invention relates to the treatment and prophylaxis of hemoglobin disorders. More particularly, the present invention provides a tailored preventative and/or maintenance treatment regimen for an individual suffering from genetic sickle cell disease.
2. Description of the Prior Art
As described in NIH Publication No. 89-2117, "Management and Therapy of Sickle Cell Disease, " 1989 herein incorporated, sickle, cell disease is a generic term for a group of genetic disorders characterized by the predominance of hemoglobin S (Hb S). These disorders include sickle cell anemia, the sickle beta thalassemia syndromes, and hemoglobinopathies in which Hb S is in association with another abnormal hemoglobin.
The two beta globin genes located on chromosome 11 and the four alpha globin genes located on chromosome 16 determine hemoglobin production. Normal red blood cells are produced in individuals who carry all four alpha globin genes and two normal beta globin genes (.beta.A). Carriers of the sickle cell trait, who do not normally physically express the disease, have a normal beta globin gene and a .beta.S globin gene, resulting in the production of both normal hemoglobin A and hemoglobin S, with a predominance of Hb A. Individuals who are homozygous for the sickle beta globin gene (.beta.S) have sickle cell anemia (Hb SS). Individuals with sickle beta thalassemia have a .beta.S gene and a gene for beta thalassemia, .beta.thal. Those who have two abnormal beta globin genes, .beta.S and .beta.C, produce hemoglobins Hb S and Hb C, and have Hb SC disease. The absence of two of the alpha globin genes results in alpha thalassemia. Abnormalities in both the beta and alpha genes may be present in the same individual.
Red blood cells of suffers of sickle cell disease are prone to distortions in geometry when deoxygenated. This distortion arises from the polymerization or gelling of Hb S molecules into elongated microtubular structures. Hb S is more susceptible to polymerization in the deoxygenated state than hemoglobin A due to the substitution of a hydrophobic residue, valine, for a polar residue glutamic acid in Hb A. These distortions of red blood cells, or sickling, leads to chronic hemolytic anemia and vasoocclusion resulting in ischemic tissue injury.
Hemolytic anemia is caused by abnormal properties of Hb S and/or by repeated cycles of sickling and unsickling, which interact to produce irreversible red cell membrane changes and erythrocyte destruction. Tissue injury is usually produced by hypoxia secondary to obstruction of blood vessels by an accumulation of sickled erythrocytes. The organs at greatest risk are those with venous sinuses where blood flow is slow and oxygen tension and pH are low (spleen, kidney, bone marrow) or those with a limited terminal arterial blood supply (eye, head of the femur). Symptoms of the hypoxic injury may be either acute (e.g., painful events, acute chest syndrome) or insidious in onset (e.g., aseptic necrosis of the hips, sickle cell retinopathy). The effects of acute and chronic tissue injury may ultimately result in organ failure, particularly as the patient ages.
In managing chronic sickle cell disease, conventional maintenance measures usually include preventative administration of antibiotics, hydration, and supplementation of dietary deficiencies. For painful events, analgesics such as aspirin, acetaminophen, ibuprofin, codeine or oxycodone may be administered. More drastic measures, such as blood transfusions or the use of compositions which change the geometry and/or oxygen binding ability of sickled red blood cells have been employed for acute indications.
The use of various vitamins, minerals, and amino acids in treating anemia related disorders has been the subject of earlier patents. For example, U.S. Pat. No. 4,945,083, issued Jul. 31, 1990 to Christian Jansen, Jr. describes a method for treating or preventing macrocytic-megaloblastic anemias with multi-factor vitamin formulations. U.S. Pat. No. 4,261,980, issued May 14, 1981 to Joseph Cort and U.S. Pat. No. 4,376,766, issued Mar. 15, 1983 to Rosalind Collinson-Jones et al. describe the use of amino acids in sickle cell treatments.
Other combination therapies for sickle cell anemia with formulations that include vitamins are described in U.S. Pat. No. 4,904,678, issued Feb. 27, 1990 to Oji Chima, and U.S. Pat. No. 5,108,754, issued Apr. 28, 1992 to Michael Wilburn. U.S. Pat. No. 4,866,052, issued Sep. 12, 1989 to Robert Hider et al. describes the use of zinc bound to various ligands, including ascorbic acid (vitamin C).
U.S. Pat. No. 5,114,972, issued May 19, 1992 to Tsuyoshi Ohnishi describes the anti-oxidant and anti-cancer activity of prostaglandin derivatives of ascorbic acid. U.S. Pat. No. 4,629,625, issued Dec. 16, 1986 to Gerald Gaull describes compositions including vitamins and/or minerals in combination with taurine, a compound synthesized in animal tissues, useful in providing a protective action on cell membranes. U.S. Pat. No. 5,364,644, issued Nov. 15, 1994 to Zbigniew Walaszek et al. describes methods for lowering cholesterol with D-glucarate which may include a multiplicity of vitamins, minerals and micronutrients.
None of the above inventions and patents, taken either singly or in combination, is seen to describe the instant invention as claimed.